Diastereoselective addition of zincated hydrazones to alkenylboronates and stereospecific trapping of boron/zinc bimetallic intermediates by carbon electrophiles.
Zincated hydrazones possessing a tert-butyl group on the zinc atom undergo addition to (E)- or (Z)-alkenylboronic acid pinacol esters to produce alpha-alkylated-gamma-boryl-gamma-zinciohydrazone intermediates with good to excellent diastereoselectivity (ds). The 1,1-organodimetallic intermediate possessing a boron atom and a zinc atom in the position gamma to the hydrazone group undergoes further C-C bond formation with a carbon electrophile to give a gamma-boryl hydrazone possessing several contiguous stereogenic centers with up to 99% ds. The (S)-1-amino-2-methoxymethylpyrrolidine hydrazone shows a high level of asymmetric induction in the addition/trapping sequence. Density functional theory calculations on the pathways of the addition reaction revealed a metallo-ene mechanism consisting of the formation of a pi complex between a zincated hydrazone and a vinylborane followed by a six-centered bond reorganization of a highly ordered boat conformation transition state. The calculations indicated that the use of the zinc atom together with the imine or hydrazone is the key for the success of the olefinic variant of the aldol reaction that has long been considered not to take place because of the endothermicity of the reaction and has never been examined with any seriousness by chemists. The steric repulsion caused by the bulky tert-butyl ligand on the zinc atom and the pinacol moiety of the vinylboronate substrates in the highly ordered transition structures gives rise to the observed high ds of the present carbozincation reaction.
Hatakeyama
Takuji
T
Department of Chemistry, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nakamura
Masaharu
M
Nakamura
Eiichi
E